title: Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine model of palladium-induced metal allergy.
abstract: Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is characterized by the recruitment of lymphocytes into sites of allergic inflammation. Because of the unavailability of suitable animal models for metal allergy, the role of T cells in the pathogenesis of metal allergy has not been explored. Thus, we developed a novel mouse model for metal allergy associated with infiltration of T cells by multiple injections of palladium (Pd) plus lipopolysaccharide into the footpad. Using this model, we characterized footpad-infiltrating T cells in terms of phenotypic markers, T cell receptor (TCR) repertoires and cytokine expression. CD3+ CD4+ T cells accumulated in the allergic footpads 7 days after Pd challenge. The expression levels of CD25, interleukin-2, interferon-γ and tumor necrosis factor, but not interleukin-4 and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T helper 1 (Th1) cells locally expanded in response to Pd. Infiltrated T cells in the footpads frequently expressed AV18-1 and BV8-2 T cell receptor (TCR) chains compared with T cells in the lymph nodes and exhibited oligoclonality. T-cell clones identified from Pd-allergic mouse footpads shared identical CDR3 sequences containing AV18-1 and BV8-2. These results suggest that TCR AV18-1 and BV8-2 play dominant and critical parts in the antigen specificity of Pd-specific Th1 cells.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, Yokohama, Japan ; Department of Rheumatology and Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Japan ; Department of Oral and Maxillofacial Surgery, Nagano Matsushiro General Hospital, Nagano, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kumagai
authors.forename: Takanori
authors.initials: T
authors.lastname: Eguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kitaura
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Kawano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Horikawa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takaji
authors.initials: T
authors.lastname: Matsutani
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hamada
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D010165:Palladium / Q000009:adverse effects*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D015415:Biomarkers; D022801:Complementarity Determining Regions; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D010165:Palladium